08/24/2011

Upsher-Smith Laboratories, Inc. announced the initiation of a Phase III clinical trial to evaluate the safety and efficacy of USL261, an investigational intranasal midazolam, for the rescue treatment of seizures in patients on stable anti-epileptic drug (AED) regimens who require control of intermittent bouts of increased seizure activity, frequently referred to as seizure clusters. USL261 has been granted orphan drug designation for this use by the Food and Drug Administration (FDA).

The Phase III randomized, double-blind, placebo-controlled study, ARTEMIS1 ["Acute Rescue Therapy in Epilepsy with Midazolam Intranasal Spray"], will compare intranasal midazolam, a benzodiazepine, with an intranasal placebo in males and females ages 14 to 65 years with a diagnosis of seizure clusters and who have a competent caregiver. The seizure clusters must have a pattern that is different from the individual's other non-cluster seizure activity and must be recognizable by a caregiver. USL261 may allow a caregiver to deliver an appropriate dose of the medication intranasally to an individual who is experiencing an intermittent bout of increased seizure activity. It is intended that this administration will not require an active inhalation by the patient.

The trial will enroll eligible patients with partial or generalized seizures who are on stable AED regimens. USL261 is the subject of a global Phase III clinical trial (ARTEMIS1), being conducted under a Special Protocol Assessment (SPA) agreement with the FDA.

There is a significant need for new therapies to manage intermittent bouts of increased seizure activity, or seizure clusters. Currently, only one medication is FDA-approved for intermittent bouts of increased seizure activity, and it must be delivered rectally.

Seizure clusters are characterized by multiple seizures which occur over a relatively brief period of time - generally within 24 hours for adults and 12 hours for children with a pattern distinguishable from the usual seizure pattern. (1) Typically there is recovery between seizures. (2) Estimates of seizure cluster prevalence vary, but it has been estimated that approximately 22% of the intractable epilepsy population (approximately 152,000 people) experience them. (3,4,5,6)

"Seizure clusters put epilepsy patients at higher risk for seizure-related emergency room visits and convulsive status epilepticus, contributing disproportionately to the health system costs associated with the disease," said Jacqueline French, MD, Director of the Clinical Trials Consortium at New York University's Comprehensive Epilepsy Center. "There is a significant need for new therapies in development, such as intranasal midazolam, that may help effectively manage intermittent bouts of increased seizure activity."

The Centers for Disease Control and Prevention estimates that epilepsy in general results in an annual cost of $15.5 billion in medical expenses and lost or reduced earnings and productivity.(7) More specifically, epilepsy patients with seizure clusters are at risk for seizure-related emergency room visits and convulsive status epilepticus (SE),(8,9) a state of prolonged seizure activity which results in an estimated 42,000 deaths and thousands of instances of brain damage each year.(10) Missed school and work, as well as greater use of health care resources, are among the socioeconomic effects of seizure clusters.(8)

"The initiation of this Phase III study further affirms Upsher-Smith's commitment to address the unmet needs of the epilepsy community," said Mark Evenstad, CEO, Upsher-Smith. "We are proud to mark this important milestone in our evolving franchise of products in development for conditions affecting the central nervous system, including epilepsy."

Upsher-Smith's Expanding CNS Pipeline

USL's central nervous system (CNS) pipeline includes a number of investigational drug programs. In addition to USL261 (intranasal midazolam), USL is developing an extended-release topiramate (USL255), as a convenient once daily treatment for adult patients with epilepsy. Another program is USL260 (tonabersat), an investigational drug and first-in-class neuronal gap junction modulator which is also a potential treatment for epilepsy.

About Epilepsy

Epilepsy is a medical condition that produces seizures affecting a variety of mental and physical functions. An estimated three million people in the U.S. have some form of epilepsy with about 200,000 new cases of epilepsy diagnosed each year.(11)

About Seizure Clusters

Seizure clusters, also referred to as acute repetitive seizures, are multiple seizures which occur over a relatively brief period of time generally within 24 hours in adults and 12 hours in children with a pattern distinguishable from the usual seizure pattern.(1) Inadequate treatment of seizure clusters can potentially impact the safety of an epilepsy patient, result in emergency room visits, and evolve into status epilepticus, a potentially life-threatening condition.(8,9,10) A previous study has suggested that seizure clustering during AED treatment may be associated with poor long-term seizure outcome and mortality.(12)